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Rajakumar A, Paulin S, Sam AF, Jothimani D, Rammohan A, Rela M. Impact of Perioperative Serum Sodium Levels on Outcomes Following Living Donor Liver Transplantation. J Clin Exp Hepatol 2025; 15:102511. [PMID: 40093507 PMCID: PMC11908579 DOI: 10.1016/j.jceh.2025.102511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 01/29/2025] [Indexed: 03/19/2025] Open
Abstract
Background & objectives Preoperative hyponatremia has been shown to be associated with poor outcomes post-liver transplantation. We analyzed the impact of preoperative hyponatremia and perioperative sodium (Na) changes on outcomes following adult living donor liver transplantation. Methods After obtaining clearance from Institutional ethical Committee, a retrospective review of electronic database and medical records of all adult patients who underwent LDLT between January 2019 and September 2022 was done and relevant perioperative data were collected. Results The study cohort of 520 recipients was divided into four groups based on preoperative serum Na levels in mmol/L; 12 patients (2.3%) in Group A (<125); 66 patients (12.6%) in Group B (125-129); 216 patients (41.5%) in Group C (130-135) and 226 patients (43.4%) in Group D (136-145). MELD score, preoperative AKI, SBP, intraoperative ascites volume, volume of packed blood cells (PRC), other blood products and 25% albumin were significantly associated with the degree of hyponatremia. No other outcomes including mortality was associated any grade of hyponatremia. The delta sodium on postoperative day 1 was largest in Group A. The level of Na rise post-transplant on POD1 had an inverse correlation with preoperative Na levels [ r (520) -0.6, P < 0.001]. High delta sodium was not associated with neurological complications in this cohort. Group A patients had higher incidence of postoperative AKI requiring dialysis followed by groups B, C and D. Eighty-six (16.5%) patients had large delta-Na of >10 mmol/L. On univariate analysis, low pretransplant Na (<130mEq/L), preoperative AKI, SBP, higher MELD and ascitic volumes, intraoperative transfusions of PRC, blood products and 25% albumin, early allograft dysfunction and need for dialysis, were associated with larger delta-Na. On multivariate analysis, preoperative Na levels ≤130 mmol/L, intraoperative ascites and PRC transfusion were found to be independent risk factors for a large delta-Na. Conclusion Hyponatremia, being a factor associated with liver disease, might not by itself contribute to poor survival when the deleterious effects of large delta changes can be avoided. The results from this study reinforces the fact that with a cautious perioperative approach, patients with hyponatremia can be transplanted safely in LDLT settings.
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Affiliation(s)
- Akila Rajakumar
- Department of Liver Intensive Care and Anaesthesia, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Susan Paulin
- Department of Liver Intensive Care and Anaesthesia, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Amal Francis Sam
- Department of Liver Intensive Care and Anaesthesia, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Dinesh Jothimani
- Department of Hepatology and Liver Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Ashwin Rammohan
- Department of HPB Surgery and Liver Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
| | - Mohamed Rela
- Department of HPB Surgery and Liver Transplantation, Dr. Rela Institute and Medical Centre, Chennai, India
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Verona P, Edwards J, Hubert K, Avorio F, Re VL, Di Stefano R, Carollo A, Johnson H, Provenzani A. Tacrolimus-Induced Neurotoxicity After Transplant: A Literature Review. Drug Saf 2024; 47:419-438. [PMID: 38353884 DOI: 10.1007/s40264-024-01398-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2024] [Indexed: 04/17/2024]
Abstract
Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection.
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Affiliation(s)
- Paige Verona
- School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
| | - Jocelyn Edwards
- School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kassidy Hubert
- School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA
| | - Federica Avorio
- Neurology Unit, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy
| | - Vincenzina Lo Re
- Neurology Unit, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy
| | - Roberta Di Stefano
- Clinical Pharmacy Service, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Via E.Tricomi n. 5, 90127, Palermo, Italy
| | - Anna Carollo
- Clinical Pharmacy Service, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Via E.Tricomi n. 5, 90127, Palermo, Italy
| | - Heather Johnson
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA, USA
| | - Alessio Provenzani
- Clinical Pharmacy Service, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Via E.Tricomi n. 5, 90127, Palermo, Italy.
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Kang M, Koh HH, Kim DG, Yim SH, Choi MC, Min EK, Lee JG, Kim MS, Joo DJ. Clinical Impact and Risk Factors of Seizure After Liver Transplantation: A Nested Case-Control Study. Transpl Int 2024; 37:12342. [PMID: 38476214 PMCID: PMC10930032 DOI: 10.3389/ti.2024.12342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 02/19/2024] [Indexed: 03/14/2024]
Abstract
Seizures are a frequent neurological consequence following liver transplantation (LT), however, research on their clinical impact and risk factors is lacking. Using a nested case-control design, patients diagnosed with seizures (seizure group) within 1-year post-transplantation were matched to controls who had not experienced seizures until the corresponding time points at a 1:5 ratio to perform survival and risk factor analyses. Seizures developed in 61 of 1,243 patients (4.9%) at median of 11 days after LT. Five-year graft survival was significantly lower in the seizure group than in the controls (50.6% vs. 78.2%, respectively, p < 0.001) and seizure was a significant risk factor for graft loss after adjusting for variables (HR 2.04, 95% CI 1.24-3.33). In multivariable logistic regression, body mass index <23 kg/m2, donor age ≥45 years, intraoperative continuous renal replacement therapy and delta sodium level ≥4 mmol/L emerged as independent risk factors for post-LT seizure. Delta sodium level ≥4 mmol/L was associated with seizures, regardless of the severity of preoperative hyponatremia. Identifying and controlling those risk factors are required to prevent post-LT seizures which could result in worse graft outcome.
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Affiliation(s)
| | | | - Deok-Gie Kim
- Department of Surgery, The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
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Janičko M, Dražilová S, Gazda J, Tomáš M, Kučera M, Šuchová Ž, Jarčuška P. Clinical Significance and Management of Hyponatremia in Liver Cirrhosis. GASTROENTEROLOGY INSIGHTS 2023; 14:446-462. [DOI: 10.3390/gastroent14040033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
The overall prevalence of hyponatremia in cirrhotics is around 50%. Hypovolemic hyponatremia is a result of excessive fluid loss caused mostly by diuretic treatment or diarrhea. More common is hypervolemic hyponatremia, which results from excessive activation of water and sodium-retaining mechanisms caused by effective arterial hypovolemia. This review focuses on the associations of hyponatremia with clinical outcomes and reviews the available data on its management. Hyponatremia is a strong predictor of mortality and is also associated with an increased probability of hepatorenal syndrome, disturbance of consciousness, infections, and unfavorable post-transplant outcomes. In the management of hyponatremia, it is crucial to distinguish between hypovolemic and hypervolemic hyponatremia. The treatment of hypervolemic hyponatremia should be started only in symptomatic patients. The cessation of the treatment with traditional diuretics and fluid restriction may prevent further decrease in natremia. Pharmacological treatment is directed towards cirrhosis itself, precipitating factor, or hyponatremia directly. Currently, only albumin infusions can be recommended routinely. Other possibilities, such as vaptans, splanchnic vasoconstrictors, niravoline, or osmotic diuretics, are restricted to specific use cases (e.g., imminent liver transplantation) or need more research to determine their efficacy. We tried to summarize the management of hyponatremia into a concise flowchart.
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Affiliation(s)
- Martin Janičko
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Sylvia Dražilová
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Jakub Gazda
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Martin Tomáš
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Martin Kučera
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Želmíra Šuchová
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
| | - Peter Jarčuška
- 2nd Department of Internal Medicine, L. Pasteur University Hospital and PJ Safarik University in Kosice, Trieda SNP 1, 04011 Kosice, Slovakia
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Khalid MB, Nagorna A, Rippel N, Ezaz G, Schiano TD, Crismale JF. Early neurologic complications after liver transplant are associated with reduced long-term survival and increased rates of rejection. Liver Transpl 2023; 29:1079-1088. [PMID: 37147847 DOI: 10.1097/lvt.0000000000000172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 04/28/2023] [Indexed: 05/07/2023]
Abstract
Neurologic complications (NCs) are common following liver transplantation (LT) and have been associated with impaired short-term survival. The impact of NC on long-term survival is less defined. We aimed to characterize these outcomes and assess for risk factors for post-LT NC. We performed a single-center, retrospective review of 521 patients with LT from 2016 to 2020. Baseline clinical and laboratory factors, intraoperative events, and outcomes were compared between patients with and without NC. The 5-year overall and rejection-free survival was estimated using the Kaplan-Meier analysis. Multivariable logistic regression assessed for an independent relationship between risk factors and the development of NC. Among 521 LT recipients, 24% experienced post-LT NC. Overall and rejection-free survival at 5 years was, respectively, 69% and 75% among those with NC versus 87% and 88% among those without NC (log-rank < 0.001). Among those who survived the first 3 months after LT, overall survival but not rejection-free survival was reduced among patients with NC. Risk factors for developing NC included peri-LT serum sodium (ΔSNa) ≥ 6 (29.4% vs. 20.5%, p = 0.04), grade 3 or 4 HE pre-LT, SNa < 125 pre-LT, and more intraoperative transfusions. In a multivariable logistic regression model controlling for described variables, SNa < 125 (or 0.21, 95% CI, 0.06-0.74) at LT and pre-LT HE grade 3 or 4 (or 0.45, 95% CI, 0.26-0.76) was independently associated with NC. Long-term survival was reduced among patients who developed NC in the immediate post-transplant period, even when censoring those who died in the first 3 months. Post-LT NC was associated with perioperative ΔSNa ≥ 6. Optimization of SNa pre-LT > 125 and limiting perioperative ΔSNa <6 mEq/L might have a beneficial impact in decreasing NC post-LT, which may improve long-term post-LT survival.
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Affiliation(s)
- Mian B Khalid
- Department of Medicine, Mount Sinai Hospital, New York, New York, USA
| | - Agnieszka Nagorna
- Department of Medicine, Mount Sinai Hospital, New York, New York, USA
| | - Noa Rippel
- Department of Medicine, Mount Sinai Hospital, New York, New York, USA
| | - Ghideon Ezaz
- Recanati/Miller Transplantation Institute, Division of Liver Disease, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - Thomas D Schiano
- Recanati/Miller Transplantation Institute, Division of Liver Disease, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | - James F Crismale
- Recanati/Miller Transplantation Institute, Division of Liver Disease, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
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Ryu JY, Baek SH, Kim S. Evidence-based hyponatremia management in liver disease. Clin Mol Hepatol 2023; 29:924-944. [PMID: 37280091 PMCID: PMC10577348 DOI: 10.3350/cmh.2023.0090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 06/05/2023] [Accepted: 06/05/2023] [Indexed: 06/08/2023] Open
Abstract
Hyponatremia is primarily a water balance disorder associated with high morbidity and mortality. The pathophysiological mechanisms behind hyponatremia are multifactorial, and diagnosing and treating this disorder remains challenging. In this review, the classification, pathogenesis, and step-by-step management approaches for hyponatremia in patients with liver disease are described based on recent evidence. We summarize the five sequential steps of the traditional diagnostic approach: 1) confirm true hypotonic hyponatremia, 2) assess the severity of hyponatremia symptoms, 3) measure urine osmolality, 4) classify hyponatremia based on the urine sodium concentration and extracellular fluid status, and 5) rule out any coexisting endocrine disorder and renal failure. Distinct treatment strategies for hyponatremia in liver disease should be applied according to the symptoms, duration, and etiology of disease. Symptomatic hyponatremia requires immediate correction with 3% saline. Asymptomatic chronic hyponatremia in liver disease is prevalent and treatment plans should be individualized based on diagnosis. Treatment options for correcting hyponatremia in advanced liver disease may include water restriction; hypokalemia correction; and administration of vasopressin antagonists, albumin, and 3% saline. Safety concerns for patients with liver disease include a higher risk of osmotic demyelination syndrome.
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Affiliation(s)
- Ji Young Ryu
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Seon Ha Baek
- Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Sejoong Kim
- Department of Internal Medicine, Seoul University Bundang Hospital, Seongnam, Korea
- Center for Artificial Intelligence in Healthcare, Seoul University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Bayona Molano MDP, Barrera Gutierrez JC, Landinez G, Mejia A, Haskal ZJ. Updates on the Model for End-Stage Liver Disease Score and Impact on the Liver Transplant Waiting List: A Narrative Review. J Vasc Interv Radiol 2023; 34:337-343. [PMID: 36539154 DOI: 10.1016/j.jvir.2022.12.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 12/07/2022] [Accepted: 12/10/2022] [Indexed: 12/23/2022] Open
Abstract
The model for end-stage liver disease (MELD) score is an established indicator of cirrhosis severity and a predictor of morbidity and mortality in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) creation and for allocation in liver transplantation. Since the adoption of the score, its use has been expanded to multiple new indications requiring model modifications, including relevant clinical and demographic variables, to increase predictive accuracy. The purpose of this report is to provide an update on the modifications made to the MELD score, comparing their performance with C statistics, advantages and disadvantages, and impact on mortality at 3 months after placing a TIPS or awaiting liver transplantation.
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Affiliation(s)
| | | | - Gina Landinez
- Interventional Radiology Section, University of California San Francisco, San Francisco, California
| | - Alejandro Mejia
- Hepatobiliary and Transplant Surgery, Methodist Dallas Medical Center, Dallas, Texas
| | - Ziv J Haskal
- Department of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, Virginia
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Correction and Prevention of Hyponatremia in Patients With Cirrhosis and Ascites: Post Hoc Analysis of the ANSWER Study Database. Am J Gastroenterol 2023; 118:168-173. [PMID: 36087106 DOI: 10.14309/ajg.0000000000001995] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/15/2022] [Indexed: 01/28/2023]
Abstract
INTRODUCTION We assessed the impact of long-term albumin administration to hyponatremic patients with ascites enrolled in the ANSWER trial. METHODS The normalization rate of baseline hyponatremia and the 18-month incidence rate of at least moderate hyponatremia were evaluated. RESULTS The hyponatremia normalization rate was higher with albumin than with standard medical treatment (45% vs 28%, P = 0.042 at 1 month). Long-term albumin ensured a lower incidence of at least moderate hyponatremia than standard medical treatment (incidence rate ratio: 0.245 [CI 0.167-0.359], P < 0.001). DISCUSSION Long-term albumin administration improves hyponatremia and reduces episodes of at least moderate hyponatremia in outpatients with cirrhosis and ascites.
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Teo CB, Gan MY, Tay RYK, Loh WJ, Loh NHW. Association of preoperative hyponatremia with surgical outcomes: a systematic review and meta-analysis of 32 observational studies. J Clin Endocrinol Metab 2022; 108:1254-1271. [PMID: 36472931 PMCID: PMC10099166 DOI: 10.1210/clinem/dgac685] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/08/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Preoperative hyponatremia is prevalent in patients undergoing surgical procedures, but it is uncertain if hyponatremia will lead to increased risk of surgical mortality and morbidity. METHODS A systematic search of Medline (PubMed), Embase and Cochrane Library from inception till 2 July 2021 was performed. Full length articles that reported on the association between surgical outcomes among adults ≥18 years with documented preoperative hyponatremia were included. FINDINGS We identified 32 observational studies comprising 1,301,346 participants. All studies had low risk of bias. When adjusted for covariates, patients with hyponatremia had significantly higher odds of developing major complications (defined as a composite measure of 9 major complications) compared to patients with normal sodium concentrations (aOR = 1.37, 95%CI = 1.23-1.53, I2 = 78%. N = 10). Additionally, patients with preoperative hyponatremia also significantly higher hazards of early mortality (<90 days) compared to patients with normonatremia (aHR = 1.27, 95%CI = 1.13-1.43, I2 = 97%. N = 10) after adjustment for covariates. Preoperative hyponatremia also had significant associations with respiratory, renal and septic complications. In terms of prognostic performance, preoperative hyponatremia performed adequately in predicting major complications in surgical patients (AUC = 0.70, LR- 0.90) with a specificity of 88% and a sensitivity of 25%. INTERPRETATION Our meta-analysis suggests that preoperative hyponatremia is associated with poorer early mortality and major morbidity outcomes in surgical patients. Hyponatremia is also a specific prognosticator for major complications in surgical patients, reiterating its potential use as a clinical indicator of poor outcomes.
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Affiliation(s)
- Chong Boon Teo
- Ministry of Health Holdings, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | - Ryan Yong Kiat Tay
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Wann Jia Loh
- Department of Endocrinology, Changi General Hospital, Singapore
| | - Ne-Hooi Will Loh
- Department of Anaesthesia, National University Hospital, Singapore
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Garcia-Saenz-de-Sicilia M, Al-Obaid L, Hughes DL, Duarte-Rojo A. Mastering Core Recommendations during HEPAtology ROUNDS in Patients with Advanced Chronic Liver Disease. Semin Liver Dis 2022; 42:341-361. [PMID: 35764316 DOI: 10.1055/a-1886-5909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Efficient and thorough care of hospitalized patients with advanced chronic liver disease is of utter importance to improve outcomes and optimize quality of life. This requires understanding current evidence and best practices. To facilitate focus on up-to-date knowledge and a practical approach, we have created the HEPA-ROUNDS mnemonic while outlining a practical review of the literature with critical appraisal for the busy clinician. The HEPA-ROUNDS mnemonic provides a structured approach that incorporates critical concepts in terms of prevention, management, and prognostication of the most common complications frequently encountered in patients with advanced chronic liver disease. In addition, implementing the HEPA-ROUNDS mnemonic can facilitate education for trainees and staff caring for patients with advanced chronic liver disease.
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Affiliation(s)
| | - Lolwa Al-Obaid
- Division of Gastroenterology, Washington University School of Medicine in St. Louis, St. Louis, Missouri
| | - Dempsey L Hughes
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Andrés Duarte-Rojo
- Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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Abstract
Hyponatremia is the most common electrolyte disorder encountered in clinical practice, and it is a common complication of cirrhosis reflecting an increase in nonosmotic secretion of arginine vasopressin as a result of of the circulatory dysfunction that is characteristic of advanced liver disease. Hyponatremia in cirrhosis has been associated with poor clinical outcomes including increased risk of morbidity and mortality, poor quality of life, and heightened health care utilization. Despite this, the treatment of hyponatremia in cirrhosis remains challenging as conventional therapies such as fluid restriction are frequently ineffective. In this review, we discuss the epidemiology, clinical outcomes, pathogenesis, etiology, evaluation, and management of hyponatremia in cirrhosis.
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Affiliation(s)
- Helbert Rondon-Berrios
- Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Juan Carlos Q. Velez
- Ochsner Clinical School/The University of Queensland, Brisbane, Queensland, Australia AND Department of Nephrology, Ochsner Health, New Orleans, Louisiana, USA
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Verbeek TA, Saner FH, Bezinover D. Hyponatremia and Liver Transplantation: A Narrative Review. J Cardiothorac Vasc Anesth 2022; 36:1458-1466. [PMID: 34144870 DOI: 10.1053/j.jvca.2021.05.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/28/2021] [Accepted: 05/12/2021] [Indexed: 11/11/2022]
Abstract
Hyponatremia is a common electrolyte disorder in patients with end-stage liver disease (ESLD) and is associated with increased mortality on the liver transplantation (LT) waiting list. The impact of hyponatremia on outcomes after LT is unclear. Ninety-day and one-year mortality may be increased, but the data are conflicting. Hyponatremic patients have an increased rate of complications and longer hospital stays after transplant. Although rare, osmotic demyelination syndrome (ODS) is a feared complication after LT in the hyponatremic patient. The condition may occur when the serum sodium (sNa) concentration increases excessively during or after LT. This increase in sNa concentration correlates with the degree of preoperative hyponatremia, the amount of intraoperative blood loss, and the volume of intravenous fluid administration. The risk of developing ODS after LT can be mitigated by avoiding large perioperative increases in sNa concentration . This can be achieved through measures such as carefully increasing the sNa pretransplant, and by limiting the intravenous intra- and postoperative amounts of sodium infused. SNa concentrations should be monitored regularly throughout the entire perioperative period.
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Affiliation(s)
- Thomas A Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health, Milton S. Hershey Medical Center/Penn State College of Medicine, Hershey, PA.
| | - Fuat H Saner
- Department of General, Visceral, and Transplantation Surgery, Essen University Medical Center, Essen, Germany
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health, Milton S. Hershey Medical Center/Penn State College of Medicine, Hershey, PA
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13
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Perioperative Delta Sodium and Post-Liver Transplant Neurological Complications in Liver Transplant Recipients. Transplantation 2022; 106:1609-1614. [PMID: 35289775 DOI: 10.1097/tp.0000000000004102] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hyponatremia before liver transplant (LT) increases risk of post-LT neurological complications in patients with decompensated cirrhosis, but it is unknown to what extent change in sodium from pre- to post-LT influences risk of central nervous system (CNS) sequelae. We assessed the relationship between pre- to post-LT delta sodium and prevalence of CNS complications during LT hospitalization. METHODS We performed retrospective single-center chart review of 1265 adults with cirrhosis who underwent LT (2011-2020). Delta sodium is defined as the difference between maximum sodium within 48 h post-LT and lowest sodium within 7 d pre-LT. Primary outcomes are post-LT CNS events during same hospitalization-encephalopathy, delirium, seizure, coma, osmotic demyelination syndrome, or other altered mental status, determined by International Classification of Diseases codes. Secondary outcome is length of hospital stay post-LT (LOS). Logistic regression modeled association between delta sodium and post-LT CNS outcomes; negative binomial regression modeled LOS. RESULTS Median age was 59 y, 36% were female, and median MELD was 20. Median delta sodium was 8 mmol/L (interquartile range, 5-11). 194 (15%) experienced post-LT CNS complications. In multivariable analysis, controlling for confounders including pre-LT hyponatremia, every 5 mmol/L increase in delta sodium associated with 47% greater odds of CNS complication (95% confidence interval, 22%-77%). Delta sodium also associated with 7% increased LOS in adjusted regression (95% confidence interval, 3%-12%). CONCLUSIONS Adult LT recipients with higher perioperative delta sodium shifts displayed a higher risk of post-LT CNS complications, even after adjusting for pre-LT sodium. LT recipients, even those with pre-LT hyponatremia, may benefit from maintenance of stable serum sodium levels to minimize post-LT CNS complications.
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Praharaj DL, Anand AC. Clinical Implications, Evaluation, and Management of Hyponatremia in Cirrhosis. J Clin Exp Hepatol 2022; 12:575-594. [PMID: 35535075 PMCID: PMC9077240 DOI: 10.1016/j.jceh.2021.09.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/06/2021] [Indexed: 02/06/2023] Open
Abstract
Hyponatremia is the most common electrolyte abnormality in patients with decompensated cirrhosis on Liver Transplantation (LT) waiting list. Most of these patients have dilutional or hypervolemic hyponatremia secondary to splanchnic vasodilatation. Excessive secretion of the antidiuretic hormone also plays an important role. Hypervolemic hyponatremia is commonly associated with refractory ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy. Although uncommon, the use of diuretics and laxatives can cause hypovolemic hyponatremia that is characterized by the striking absence of ascites or pedal edema. Clinical features are often nonspecific and depend on the acuity of onset rather than the absolute value of serum sodium. Symptoms may be subtle, including nausea, lethargy, weakness, or anorexia. However, rarely patients may present with confusion, seizures, psychosis, or coma. Treatment includes discontinuation of diuretics, beta-blockers, and albumin infusion. Hypertonic saline (3%) infusion may be used in patients with very low serum sodium (<110 mmol/L) or when patients present with seizures or coma. Short-term use of Vasopressin (V2) receptor antagonists may also be used to normalize sodium levels prior to LT. However, all these measures may be futile, and LT remains the definite treatment in these patients to improve survival. In this review, we describe the classification, pathogenesis of hyponatremia, and its clinical implications in patients with cirrhosis. Approach to these patients along with management will also be discussed briefly.
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Key Words
- ACE, angiotensin-converting enzyme
- ACLF, acute-on-chronic liver failure
- ACTH, adrenocorticotropic hormone
- ADH
- ADH, antidiuretic hormone
- AKI, acute kidney injury
- AVP, arginine vasopressin
- CLIF, chronic liver failure
- CNS, central nervous system
- CTP, Child-Turcotte-Pugh
- CVVHD, continuous venovenous hemofiltration
- DAMP, damage-associated molecular patterns
- EABV, effective arterial blood volume
- FENa, fractional excretion of sodium
- HE, hepatic encephalopathy
- HRS, hepatorenal syndrome
- LT, liver transplantation
- LVP, large volume paracentesis
- MAP, mean arterial pressure
- MELD, model of end-stage liver disease
- NO, nitric oxide
- NSBB, nonselective beta-blockers
- PAMP, pathogen-associated molecular patterns
- PICD, paracentesis-induced circulatory dysfunction
- PPCD, post-paracentesis circulatory dysfunction
- PRA, plasma renin activity
- RA, refractory ascites
- RAAS, renin-angiotensin-aldosterone-system
- RAI, relative adrenal insufficiency
- RBF, renal blood flow
- SBP, spontaneous bacterial peritonitis
- SIADH, syndrome of inappropriate ADH secretion
- SMT, standard medical treatment
- SNS, sympathetic nervous system
- TBW, total body water
- TIPS, transjugular intrahepatic portosystemic shunt
- advanced cirrhosis
- albumin
- hyponatremia
- liver transplantation
- sNa, serum sodium
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Affiliation(s)
- Dibya L. Praharaj
- Address for correspondence. Dibya L Praharaj, Assistant Professor, Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Science, Bhubaneswar, India
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15
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Sastre L, Crespo G. Neurotoxicity after liver transplantation: does donor age matter? Transl Gastroenterol Hepatol 2021; 6:66. [PMID: 34805588 DOI: 10.21037/tgh.2020.01.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 01/15/2020] [Indexed: 11/06/2022] Open
Affiliation(s)
- Lydia Sastre
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
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16
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Ivanics T, Leonard-Murali S, Mouzaihem H, Moonka D, Kitajima T, Yeddula S, Shamaa MT, Rizzari M, Collins K, Yoshida A, Abouljoud M, Nagai S. Extreme hyponatremia as a risk factor for early mortality after liver transplantation in the MELD-sodium era. Transpl Int 2021; 34:2856-2868. [PMID: 34580929 DOI: 10.1111/tri.14123] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 08/17/2021] [Accepted: 09/20/2021] [Indexed: 01/15/2023]
Abstract
The impact of hyponatremia on waitlist and post-transplant outcomes following the implementation of MELD-Na-based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD-Na-based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre-MELD-Na and post-MELD-Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120 mEq/l. Ninety-day waitlist outcomes and post-LT survival were compared using Fine-Gray proportional hazard and mixed-effects Cox proportional hazard models. A total of 118 487 patients were eligible (n = 64 940: pre-MELD-Na; n = 53 547: post-MELD-Na). In the pre-MELD-Na era, extreme hyponatremia at listing was associated with an increased risk of 90-day waitlist mortality ([ref: 135-145] HR: 3.80; 95% CI: 2.97-4.87; P < 0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38-2.01; P < 0.001). In the post-MELD-Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60-3.23; P < 0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76-2.55; P < 0.001) as patients with normal serum sodium levels (135-145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365-day post-LT survival compared to patients with normal serum sodium levels. With the introduction of MELD-Na-based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short-term post-LT survival.
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Affiliation(s)
- Tommy Ivanics
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | | | - Hassan Mouzaihem
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Dilip Moonka
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI, USA
| | - Toshihiro Kitajima
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Sirisha Yeddula
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Mhd Tayseer Shamaa
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Michael Rizzari
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Kelly Collins
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Atsushi Yoshida
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Marwan Abouljoud
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Shunji Nagai
- Division of Transplant and Hepatobiliary Surgery, Henry Ford Hospital, Detroit, MI, USA
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17
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Mahiliavets EV, Bozhko YN, Mahiliavets ON. Use of laparocentesis in the treatment of ascites in patients with liver cirrhosis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF BELARUS, MEDICAL SERIES 2021; 18:362-374. [DOI: 10.29235/1814-6023-2021-18-3-362-374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Ascites occurs in about 60 % of patients with cirrhosis within 10 years of diagnosis. Laparocentesis is the preferred first-line therapy in patients with cirrhosis and massive tense ascites, allowing more than 5–6 liters of ascitic fluid to be removed at one time. The search for informative prognostic factors and the development of a method for predicting unfavorable outcomes of repeated laparocenteses in patients with ascites are relevant to timely refer this contingent of patients to perform TIPS.The purpose of the study was to develop and evaluate the diagnostic significance of a model for determining the probability of unfavorable outcomes of laparocentesis in patients with ascites on the background of liver cirrhosis.The results of treatment of 99 patients with the ascitic syndrome associated with intrahepatic portal hypertension were studied. The multiple regression analysis using the binary response logit model was carried out to calculate the prediction models. The analysis of the treatment results of patients with liver cirrhosis and ascites by the laparocentesis method revealed a number of factors that influence the onset of an unfavorable outcome. 2 models with the inclusion of initial variables are the most promising for forecasting. Model A includes: patient weight, serum-ascites total protein gradient, hyponatremia; model B: MELD-Na score, serum-ascitic total protein gradient, patient weight. The developed prediction method is highly informative, effective, easily applicable, and can be widely used in clinical practice.The ability to predict an unfavorable outcome in patients with portal hypertension and ascites after laparocentesis allows for a personalized approach in the process of timely selection of more effective, but also more expensive treatment methods, such as TIPS, which will help us to increase the therapy effectiveness and the survival of this cohort of patients.
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18
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Zamberg I, Maillard J, Assouline B, Tomala S, Keli-Barcelos G, Aldenkortt F, Mavrakanas T, Andres A, Schiffer E. Perioperative Evolution of Sodium Levels in Cirrhotic Patients Undergoing Liver Transplantation: An Observational Cohort and Literature Review. Hepat Med 2021; 13:71-82. [PMID: 34393524 PMCID: PMC8357403 DOI: 10.2147/hmer.s320127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 07/08/2021] [Indexed: 11/23/2022] Open
Abstract
Background & Aims Hyponatremia is an important predictor of early death among cirrhotic patients in the orthotopic liver transplantation (OLT) waiting list. Evidence exists that prioritizing OLT waiting list according to the MELD score combined with plasma sodium concentration might prevent pre transplantation death. However, the evolution of plasma sodium concentrations during the perioperative period of OLT is not well known. We aimed to describe the evolution of perioperative sodium concentration during OLT and its relation to perioperative neurohormonal responses. Methods Twenty-seven consecutive cirrhotic patients who underwent OLT were prospectively included in the study over a period of 27 months. We studied the evolution of plasma sodium levels, the hemodynamics, the neurohormonal response and other biological markers during the perioperative period of OLT. Results Among study's population, four patients had hyponatremia before OLT, all with Child cirrhosis. In patients with hyponatremia, plasmatic sodium reached normal levels during surgery, and sodium levels remained within normal ranges 1 day, 7 days, as well as 6 months after surgery for all patients. Creatinine clearance was decreased significantly during the perioperative period, while creatinine and cystatin C levels increased significantly. Neutrophil gelatinase-associated lipocalin (NGAL) and vasopressin levels did not change significantly in this period. Plasma renin activity, concentrations of norepinephrine and brain natriuretic peptide varied significantly during the perioperative period. Conclusion In our study, plasmatic sodium concentrations among hyponatremic cirrhotic patients undergoing OLT seem to reach normal levels after OLT and remain stable six months after surgery providing more evidence for the importance of sodium levels in prioritization of liver transplant candidates. Further investigation of rapid correction and stabilization of sodium levels after OLT, as observed in our study, would be of interest in order to fully understand the mechanisms involved in cirrhosis-related hyponatremia, its prognostic value and clinical implications.
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Affiliation(s)
- Ido Zamberg
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine University of Geneva, Geneva, Switzerland
| | - Julien Maillard
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Benjamin Assouline
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Simon Tomala
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Gleicy Keli-Barcelos
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Florence Aldenkortt
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Thomas Mavrakanas
- Faculty of Medicine University of Geneva, Geneva, Switzerland.,Department of Medicine, McGill University Health Centre, Montreal, QC, Canada
| | - Axel Andres
- Faculty of Medicine University of Geneva, Geneva, Switzerland.,Division of Transplantation, Department of Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Eduardo Schiffer
- Division of Anesthesiology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine University of Geneva, Geneva, Switzerland
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19
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Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 74:1014-1048. [PMID: 33942342 DOI: 10.1002/hep.31884] [Citation(s) in RCA: 440] [Impact Index Per Article: 110.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/07/2021] [Indexed: 12/13/2022]
Affiliation(s)
- Scott W Biggins
- Division of Gastroenterology and Hepatology, and Center for Liver Investigation Fostering discovEryUniversity of WashingtonSeattleWA
| | - Paulo Angeli
- Unit of Hepatic Emergencies and Liver TransplantationDepartment of MedicineDIMEDUniversity of PadovaPaduaItaly
| | - Guadalupe Garcia-Tsao
- Department of Internal MedicineSection of Digestive DiseasesYale UniversityNew HavenCT
- VA-CT Healthcare SystemWest HavenCT
| | - Pere Ginès
- Liver Unit, Hospital Clinic, and Institut d'Investigacions Biomèdiques August Pi i SunyerUniversity of BarcelonaBarcelonaSpain
- Centro de Investigación Biomèdica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
| | - Simon C Ling
- The Hospital for Sick Children, Division of Gastroenterology, Hepatology and Nutrition, and Department of PaediatricsUniversity of TorontoTorontoOntarioCanada
| | - Mitra K Nadim
- Division of NephrologyUniversity of Southern CaliforniaLos AngelesCA
| | - Florence Wong
- Division of Gastroenterology and HepatologyUniversity Health NetworkUniversity of TorontoTorontoOntarioCanada
| | - W Ray Kim
- Division of Gastroenterology and HepatologyStanford UniversityPalo AltoCA
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20
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Crismale JF, Huisman T, Deshpande R, Law C, Im GY, Bronster D, DeMaria S, Florman S, Schiano TD. A protocol for the management of hyponatremia peri‐liver transplant reduces post‐transplant neurological complications. Clin Transplant 2021; 35:e14276. [DOI: 10.1111/ctr.14276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 11/28/2020] [Accepted: 02/19/2021] [Indexed: 12/18/2022]
Affiliation(s)
- James F. Crismale
- Recanati/Miller Transplantation InstituteThe Mount Sinai Hospital New York NY USA
| | - Tsipora Huisman
- Department of Medicine Division of Gastroenterology The Mount Sinai Hospital New York NY USA
| | - Richa Deshpande
- Department of Population Health Science and Policy Center for BiostatisticsThe Icahn School of Medicine at Mount Sinai Hospital New York NY USA
| | - Cindy Law
- Department of Medicine Division of Gastroenterology and Hepatology Rutgers‐Robert Wood Johnson Medical School New Brunswick NJ USA
| | - Gene Y. Im
- Recanati/Miller Transplantation InstituteThe Mount Sinai Hospital New York NY USA
| | - David Bronster
- Department of Neurology The Mount Sinai Hospital New York NY USA
| | - Samuel DeMaria
- Department of Anesthesiology The Mount Sinai Hospital New York NY USA
| | - Sander Florman
- Recanati/Miller Transplantation InstituteThe Mount Sinai Hospital New York NY USA
| | - Thomas D. Schiano
- Recanati/Miller Transplantation InstituteThe Mount Sinai Hospital New York NY USA
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21
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Goudsmit BFJ, Putter H, Tushuizen ME, de Boer J, Vogelaar S, Alwayn I, van Hoek B, Braat AE. Validation of the Model for End-stage Liver Disease sodium (MELD-Na) score in the Eurotransplant region. Am J Transplant 2021; 21:229-240. [PMID: 32529758 PMCID: PMC7818465 DOI: 10.1111/ajt.16142] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/12/2020] [Accepted: 06/08/2020] [Indexed: 01/25/2023]
Abstract
The MELD score is used in the Eurotransplant (ET) region to allocate liver grafts. Hyponatremia in cirrhotic patients is an important predictor of death but is not incorporated in MELD. This study investigated the performance of the MELD-Na score for the ET region. All adult patients with chronic liver disease on the ET liver transplantation waiting list (WL) allocated through lab MELD scores were included. The MELD-corrected effect of serum sodium (Na) concentration at listing on the 90-day WL mortality was calculated using Cox regression. The MELD-Na performance was assessed with c-indices, calibration per decile and Brier scores. The reclassification from MELD to MELD-Na score was calculated to estimate the impact of MELD-Na-based allocation in the ET region. For the 5223 included patients, the risk of 90-day WL death was 2.9 times higher for hyponatremic patients. The MELD-Na had a significantly higher c-index of 0.847 (SE 0.007) and more accurate 90-day mortality prediction compared to MELD (Brier score of 0.059 vs 0.061). It was estimated that using MELD-Na would reduce WL mortality by 4.9%. The MELD-Na score yielded improved prediction of 90-day WL mortality in the ET region and using MELD-Na for liver allocation will very likely reduce WL mortality.
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Affiliation(s)
- Ben F. J. Goudsmit
- Division of TransplantationDepartment of Surgery, Leiden University Medical CentreLeidenThe Netherlands,Eurotransplant International FoundationLeidenThe Netherlands,Division of TransplantationDepartment of Gastroenterology and Hepatology, Leiden University Medical CentreLeidenThe Netherlands
| | - Hein Putter
- Department of Biomedical Data SciencesLeidenThe Netherlands
| | - Maarten E. Tushuizen
- Division of TransplantationDepartment of Gastroenterology and Hepatology, Leiden University Medical CentreLeidenThe Netherlands
| | - Jan de Boer
- Eurotransplant International FoundationLeidenThe Netherlands
| | - Serge Vogelaar
- Eurotransplant International FoundationLeidenThe Netherlands
| | - I.P.J. Alwayn
- Division of TransplantationDepartment of Surgery, Leiden University Medical CentreLeidenThe Netherlands
| | - Bart van Hoek
- Division of TransplantationDepartment of Gastroenterology and Hepatology, Leiden University Medical CentreLeidenThe Netherlands
| | - Andries E. Braat
- Division of TransplantationDepartment of Surgery, Leiden University Medical CentreLeidenThe Netherlands
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22
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Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium. J Hepatol 2021; 74:200-219. [PMID: 32896580 DOI: 10.1016/j.jhep.2020.08.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 07/09/2020] [Accepted: 08/02/2020] [Indexed: 12/15/2022]
Abstract
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
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23
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Lenci I, Milana M, Grassi G, Signorello A, Aglitti A, Baiocchi L. Natremia and liver transplantation: The right amount of salt for a good recipe. World J Hepatol 2020; 12:919-930. [PMID: 33312419 PMCID: PMC7701977 DOI: 10.4254/wjh.v12.i11.919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 09/19/2020] [Accepted: 09/27/2020] [Indexed: 02/06/2023] Open
Abstract
An adequate balance between electrolytes and clear water is of paramount importance to maintaining physiologic homeostasis. Natremia imbalance and, in particular, hyponatremia is the most frequent electrolyte abnormality observed in hospitalized subjects, involving approximately one-fourth of them. Pathological changes occurring during liver cirrhosis predispose patients to an increased risk of sodium imbalance, and hypervolemic hyponatremia has been reported in nearly 50% of subjects with severe liver disease and ascites. Splanchnic vasodilatation, portal-systemic collaterals' opening and increased excretion of vasoactive modulators are all factors impairing clear water handling during liver cirrhosis. Of concern, sodium imbalance has been consistently reported to be associated with increased risk of complications and reduced survival in liver disease patients. In the last decades clinical interest in sodium levels has been also extended in the field of liver transplantation. Evidence that [Na+] in blood is an independent risk factor for in-list mortality led to the incorporation of sodium value in prognostic scores employed for transplant priority, such as model for end-stage liver disease-Na and UKELD. On the other hand, severe hyponatremic cirrhotic patients are frequently delisted by transplant centers due to the elevated risk of mortality after grafting. In this review, we describe in detail the relationship between sodium imbalance and liver cirrhosis, focusing on its impact on peritransplant phases. The possible therapeutic approaches, in order to improve transplant outcome, are also discussed.
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Affiliation(s)
- Ilaria Lenci
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Martina Milana
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Giuseppe Grassi
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Alessandro Signorello
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Andrea Aglitti
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy
| | - Leonardo Baiocchi
- Department of Internal Medicine, Hepatology Unit, Tor Vergata University, Rome 00133, Italy.
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24
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Hyponatremia Is Associated With Increased Mortality in Children on the Waiting List for Liver Transplantation. Transplant Direct 2020; 6:e604. [PMID: 33134484 PMCID: PMC7591120 DOI: 10.1097/txd.0000000000001050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 07/13/2020] [Accepted: 07/14/2020] [Indexed: 12/21/2022] Open
Abstract
Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT).
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25
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Abstract
Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal hypertension. Although not apparent in the early stages of cirrhosis, the progression of cirrhosis and portal hypertension leads to splanchnic vasodilation, and this leads to the activation of compensatory mechanisms such as renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and antidiuretic hormone (ADH) to ameliorate low circulatory volume. The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume, resulting in the development of ascites. These compensatory mechanisms lead to impairment of the kidneys to eliminate solute-free water in decompensated cirrhosis. Nonosmotic secretion of antidiuretic hormone (ADH), also known as arginine vasopressin, further worsens excess water retention and thereby hyponatremia. The management of hyponatremia in this setting is a challenge as conventional therapies for hyponatremia including fluid restriction and correction of hypokalemia are frequently inefficacious. In this review, we discuss the pathophysiology, complications, and various treatment modalities, including albumin infusion, selective vasopressin receptor antagonists, or hypertonic saline for patients with severe hyponatremia and those awaiting liver transplantation.
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Affiliation(s)
- Joseph J. Alukal
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA
| | - Savio John
- Division of Gastroenterology, Department of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Paul J. Thuluvath
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, Maryland, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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26
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Piano S, Tonon M, Angeli P. Ascites, Hyponatremia, Spontaneous Bacterial Peritonitis, and Hepatorenal Syndrome. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:662-675. [DOI: 10.1002/9781119211419.ch43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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27
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Tasdogan BE, Akosman S, Gurakar M, Simsek C, Gurakar A. Update on Liver Transplantation: What is New Recently? Euroasian J Hepatogastroenterol 2019; 9:34-39. [PMID: 31988865 PMCID: PMC6969330 DOI: 10.5005/jp-journals-10018-1293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Liver transplantation (LT) is an evolving area of medicine for the treatment of certain types of malignancies and acute and chronic liver failures. Since the topic is evolving, new literature is increasingly available. In recent years, with the emerging potent antiviral therapies, hepatitis C virus-infected patients have successful patient and graft survival outcomes. Even human immunodeficiency virus (HIV) positive patients previously contraindicated for organ transplantation are transplanted with comparable outcomes. With increasing demand for LT, the shortage of the donor pool became the rate limiting factor in this hopeful treatment. To overcome waitlist mortality and expand the donor pool, scoring systems have been modified and organs from HIV and/or hepatitis C infected donors are now accepted, under certain circumstances. The new literature also questions the 6-month alcohol abstinence rule for the transplantation of alcoholic liver disease (ALD), in light of early transplantation results from severe alcoholic hepatitis (SAH) trials. How to cite this article: Tasdogan BE, Akosman S, et al. Update on Liver Transplantation: What is New Recently? Euroasian J Hepatogastroenterol 2019;9(1):34-39.
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Affiliation(s)
- Burcak E Tasdogan
- The Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology, Baltimore, Maryland, United States
| | - Sinan Akosman
- The Johns Hopkins University, Baltimore, Maryland, United States
| | - Merve Gurakar
- The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, United States
| | - Cem Simsek
- The Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology, Baltimore, Maryland, United States
| | - Ahmet Gurakar
- The Johns Hopkins University School of Medicine, Division of Gastroenterology and Hepatology, Baltimore, Maryland, United States
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Bernardi M, Zaccherini G, Caraceni P. Pro: The Role of Albumin in Pre-Liver Transplant Management. Liver Transpl 2019; 25:128-134. [PMID: 30346096 DOI: 10.1002/lt.25356] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 10/10/2018] [Indexed: 02/07/2023]
Abstract
The wait-list mortality of patients with decompensated cirrhosis awaiting liver transplantation remains elevated due to the occurrence of complications. Etiologic treatments improve patient survival and lower the incidence of complications when applied in compensated cirrhosis, but a decompensated disease does not improve or even progress despite a response to therapy in a substantial number of patients. Thus, disease-modifying treatments that reduce the incidence of complications and improve survival are most needed. Such treatments should be able to counteract one or possibly more pathophysiological mechanisms and thus lead to the proinflammatory and pro-oxidant milieu that characterizes decompensated cirrhosis. In this respect, albumin represents a potentially ideal agent. In fact, besides its ability to expand plasma volume, albumin possesses nononcotic properties, exerting potent antioxidant and immune-modulating effects. Recent studies have assessed the effect of longterm albumin administration in decompensated cirrhosis. Although the results of these studies may appear conflicting, their analyses suggest that albumin, if given in a sufficient amount and for a sufficient duration, can significantly reduce the incidence of life-threatening complications of cirrhosis and patient mortality. For these reasons, we favor albumin administration to patients with decompensated cirrhosis wait-listed for liver transplantation.
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Affiliation(s)
- Mauro Bernardi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Intraoperative hyponatremia is an independent predictor of one-year mortality after liver transplantation. Sci Rep 2018; 8:18023. [PMID: 30575797 PMCID: PMC6303312 DOI: 10.1038/s41598-018-37006-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 11/25/2018] [Indexed: 01/15/2023] Open
Abstract
Preoperative hyponatremia is associated with an increased risk of mortality on the liver transplantation (LT) waiting list. We sought to investigate the impact of pre- and intraoperative serum sodium levels on the one-year mortality after LT. We identified 1,164 patients for whom preoperative and intraoperative serum sodium levels were available. Cox regression analysis with multivariable adjustment was performed for one-year mortality. A propensity score matching analysis was performed for preoperative and intraoperative serum sodium groups to compare one-year survival. The cutoff of sodium level with minimal p-value was 130 mEq/L for both preoperative and intraoperative sodium. Intraoperative hyponatremia was an independent predictor of one-year mortality in the multivariable Cox regression analysis, while preoperative hyponatremia was not. Kaplan-Meier curve showed that there was a significant difference in the one-year mortality between preoperative and intraoperative serum sodium groups. However, after propensity score matching, there was no difference in the one-year mortality among the preoperative sodium groups, while there was a significant difference among the intraoperative sodium groups. Intraoperative hyponatremia defined by mean sodium <130 mEq/L was independently associated with a significantly high one-year mortality. Mean intraoperative serum sodium levels may be a better prognostic predictor than preoperative serum sodium levels.
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30
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Solà E, Solé C, Simón-Talero M, Martín-Llahí M, Castellote J, Garcia-Martínez R, Moreira R, Torrens M, Márquez F, Fabrellas N, de Prada G, Huelin P, Lopez Benaiges E, Ventura M, Manríquez M, Nazar A, Ariza X, Suñé P, Graupera I, Pose E, Colmenero J, Pavesi M, Guevara M, Navasa M, Xiol X, Córdoba J, Vargas V, Ginès P. Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial. J Hepatol 2018; 69:1250-1259. [PMID: 30138685 DOI: 10.1016/j.jhep.2018.08.006] [Citation(s) in RCA: 165] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 08/06/2018] [Accepted: 08/08/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT. METHODS A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels. RESULTS There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly. CONCLUSIONS In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival. LAY SUMMARY Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.
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Affiliation(s)
- Elsa Solà
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Cristina Solé
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | | | - Marta Martín-Llahí
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - José Castellote
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Liver Unit, Gastroenterology Department, Hospital Universitari de Bellvitge, Institut Català de la Salut, L'Hospitalet de Llobregat, Barcelona, Spain; Grup de Recerca en malalties hepato-bilio-pancreàtiques, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Rita Garcia-Martínez
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Rebeca Moreira
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Maria Torrens
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Francisca Márquez
- Liver Unit, Gastroenterology Department, Hospital Universitari de Bellvitge, Institut Català de la Salut, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Núria Fabrellas
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Gloria de Prada
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Patrícia Huelin
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Eva Lopez Benaiges
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | | | - Marcela Manríquez
- Institut d'Investigació Mèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Clinical Research Support Unit, Hospital Universitari de Bellvitge, L'Hospitalet de LLobregat, Barcelona, Spain
| | - André Nazar
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Xavier Ariza
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Pilar Suñé
- Clinical Trials Unit, Pharmacy Department, Hospital Vall d'Hebron, Barcelona, Spain
| | - Isabel Graupera
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Jordi Colmenero
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Marco Pavesi
- Data Management Center, EF-CLIF, Barcelona, Spain
| | - Mónica Guevara
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
| | - Xavier Xiol
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Liver Unit, Gastroenterology Department, Hospital Universitari de Bellvitge, Institut Català de la Salut, L'Hospitalet de Llobregat, Barcelona, Spain; Grup de Recerca en malalties hepato-bilio-pancreàtiques, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Joan Córdoba
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain; Liver Unit, Hospital Vall d'Hebron, Barcelona, Spain
| | - Victor Vargas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain; Liver Unit, Hospital Vall d'Hebron, Barcelona, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
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Leise M, Cárdenas A. Hyponatremia in Cirrhosis: Implications for Liver Transplantation. Liver Transpl 2018; 24:1612-1621. [PMID: 30129266 DOI: 10.1002/lt.25327] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 07/18/2018] [Accepted: 08/08/2018] [Indexed: 12/14/2022]
Abstract
Hyponatremia in cirrhosis is defined as a serum sodium level ≤130 mEq/L and occurs in approximately 22% of patients with cirrhosis. The appearance of hyponatremia in patients with cirrhosis portends a poor prognosis before liver transplantation (LT), independent of the Model for End-Stage Liver Disease (MELD) score. With the development of the MELD-sodium score, the management of hyponatremia has become more relevant than ever before. Overcorrection of hyponatremia before LT or perioperatively can lead to the devastating neurologic condition known as osmotic demyelination syndrome, which is often irreversible and fatal. Therefore, the most important tenet of hyponatremia is to avoid correcting the serum sodium by ≥8 mEq/L in a 24-hour period. Treatment of hyponatremia is highly challenging. The vast majority of patients with cirrhosis have chronic hypervolemic hyponatremia. Fluid restriction increases serum sodium levels, but tolerance and compliance are significant barriers. Diuretic withdrawal is helpful but contributes to worsening fluid overload. There are limited data to support use of intravenous concentrated albumin solutions. The use of the arginine vasopressin antagonists ("vaptans") is contentious; however, they may have a limited role. Risk factors for intraoperative overcorrection of serum sodium include increased utilization of packed red blood cell and fresh frozen plasma transfusions, which are often unavoidable. Intraoperative management is evolving, and more data are needed in regard to the use of sodium-reduced continuous venovenous hemofiltration and the use of trishydroxymethylaminomethane (Tris) to avoid excess sodium rebound. A thorough discussion of the current treatment options before and during LT is given in this review.
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Affiliation(s)
- Michael Leise
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.,William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Andrés Cárdenas
- GI/Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, University of Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi Sunyer, Ciber de Enfermedades Hepáticas y Digestivas, Barcelona, Spain
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32
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Bernardi M, Zaccherini G. Approach and management of dysnatremias in cirrhosis. Hepatol Int 2018; 12:487-499. [PMID: 30203382 DOI: 10.1007/s12072-018-9894-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 08/28/2018] [Indexed: 12/19/2022]
Abstract
Hypervolemic (dilutional) hyponatremia is the most common dysnatremia in cirrhosis, with a prevalence close to 50% in patients with ascites, while hypovolemic hyponatremia occurs in a minority of cases. Hyponatremia carries a poor prognosis, being associated with increased mortality and reduced survival after liver transplantation. Hypernatremia is rarer and is also associated with an adverse prognosis. Increased non-osmotic secretion of arginine vasopressin and altered renal tubular sodium handling due to impaired free water generation are the mechanisms leading to hypervolemic hyponatremia, while diuretic-induced fluid loss is the main cause of hypovolemic hyponatremia. Hypernatremia usually follows hypotonic fluid losses due to osmotic diuresis (glycosuria) or lactulose-induced diarrhea. The main clinical manifestations of dysnatremias are due to their effects on the central nervous system: astroglial cell hyperhydration follows hyponatremia-an abnormality that exacerbates ammonia neurotoxicity-while the opposite abnormality occurs with hypernatremia. Asymptomatic or mildly symptomatic hypervolemic hyponatremia is mainly managed by correcting of precipitating factors and non-osmotic fluid restriction. Severe, life-threatening hyponatremia requires hypertonic saline infusion, avoiding rapid and complete correction of serum sodium concentration to prevent neurological sequelae such as osmotic demyelination. V2 receptor blockade by vaptans may be considered in patients with sustained hyponatremia waitlisted for liver transplantation. Diuretic withdrawal and plasma volume expansion are required in hypovolemic hypernatremia. Prompt recognition, removal of the precipitating factor(s) and non-osmotic fluid administration represent the mainstays of hypernatremia management. Rapid correction of long-standing hypernatremia can lead to cerebral edema and has to be avoided.
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Affiliation(s)
- Mauro Bernardi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Policlinico S. Orsola-Malpighi, Via Albertoni, 15, 40138, Bologna, Italy.
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Policlinico S. Orsola-Malpighi, Via Albertoni, 15, 40138, Bologna, Italy
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Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1781] [Impact Index Per Article: 254.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
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34
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Utility of Tolvaptan in the Perioperative Management of Severe Hyponatremia During Liver Transplantation: A Case Report. Transplant Proc 2018; 49:2399-2401. [PMID: 29198689 DOI: 10.1016/j.transproceed.2017.09.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 09/23/2017] [Indexed: 12/27/2022]
Abstract
Severe hyponatremia can complicate the pretransplantation management of patients with decompensated cirrhosis while they await liver transplantation. Before the liver transplant, it is critical to correct severe hyponatremia to an appropriate level to reduce the risks of perioperative complications such as central pontine myelinolysis, cerebral edema, and seizures. Vasopressin receptor antagonists, and in particular tolvaptan, offer a therapeutic modality that can correct severe refractory hyponatremia in a timely and predictable manner before liver transplantation. In this case report, we describe a patient with decompensated cirrhosis and severe hyponatremia in whom administration of tolvaptan led to an optimal correction of preoperative severe hyponatremia and allowed for successful liver transplantation with no associated postoperative complications. In light of the increasing pretransplantation disease severity and higher risk of severe hyponatremia, the use of tolvaptan in the pretransplant period may gain increasing importance as a therapeutic intervention for maintaining peritransplant sodium homeostasis.
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35
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Lenci I, Milana M, Angelico M, Baiocchi L. Short-Term, Low-Dose Use of Tolvaptan as a Bridge Therapy to Expedite Liver Transplant for Severe Hyponatremic, Cirrhotic Patients With High Model for End-Stage Liver Disease Scores. EXP CLIN TRANSPLANT 2017; 15:689-692. [PMID: 26581411 DOI: 10.6002/ect.2015.0209] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
For patients on liver transplant waiting lists, hyponatremia is associated with increased mortality before transplant and complications during the early posttransplant period. Conventional therapies, such as fluid restriction or hypertonic saline infusion, are of limited value. We describe 2 patients with high Model for End-Stage Liver Disease scores (> 30) who were referred to our unit for expedited liver transplant. While on waiting lists, these patients developed severe hyponatremia (< 125 mEq/L) that was refractory to conventional therapies. Low-dose, short-term tolvaptan therapy (15 mg/d for 5 d) was then administered, as a bridge therapy to transplant, resulting in prompt restoration of serum sodium levels without any major clinical event. One patient died a few days later as no suitable grafts were available. The other received a liver transplant, and the outcome was uneventful. In conclusion, our report demonstrates that a short-term, low-dose tolvaptan-based strategy promptly resolves hyponatremia in patients who are on expedited waiting lists for liver transplant, allowing surgery with improved sodium levels and possibly limiting peritransplant complications.
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Affiliation(s)
- Ilaria Lenci
- From the Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome, Italy
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36
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Jiménez JV, Carrillo-Pérez DL, Rosado-Canto R, García-Juárez I, Torre A, Kershenobich D, Carrillo-Maravilla E. Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach. Dig Dis Sci 2017; 62:1855-1871. [PMID: 28501971 DOI: 10.1007/s10620-017-4597-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 04/26/2017] [Indexed: 12/17/2022]
Abstract
Electrolyte and acid-base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid-base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid-base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid-base spectrum. Because most electrolyte and acid-base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.
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Affiliation(s)
- José Víctor Jiménez
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico
| | - Diego Luis Carrillo-Pérez
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico
| | - Rodrigo Rosado-Canto
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico
| | - Ignacio García-Juárez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico
| | - Aldo Torre
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico
| | - David Kershenobich
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico
| | - Eduardo Carrillo-Maravilla
- Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, 14080, Mexico City, Mexico.
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Leise MD, Findlay JY. Hyponatremia in the perioperative period: When and how to correct. Clin Liver Dis (Hoboken) 2017; 9:111-114. [PMID: 30992972 PMCID: PMC6467151 DOI: 10.1002/cld.630] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 12/22/2016] [Accepted: 01/28/2017] [Indexed: 02/04/2023] Open
Affiliation(s)
- Michael D. Leise
- William J. von Liebig Center for Transplantation and Clinical Regeneration,Division of Gastroenterology & Hepatology
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Kalafateli M, Zisimopoulos K, Vourli G, Rigamonti C, Goulis J, Manesis E, Manolakopoulos S, Tsochatzis E, Georgiou A, Diamantopoulou G, Thomopoulos K, Gogos C, Touloumi G, Akriviadis E, Lambropoulou-Karatza C, Triantos C. Prognostic Models for Survival in Patients with Stable Cirrhosis: A Multicenter Cohort Study. Dig Dis Sci 2017; 62:1363-1372. [PMID: 28251503 DOI: 10.1007/s10620-017-4504-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Accepted: 02/13/2017] [Indexed: 12/29/2022]
Abstract
BACKGROUND Two models are mostly used to predict survival in cirrhosis: the Child-Pugh score (CP score) and the model for end-stage liver disease score (MELD score). AIMS The aim of this study is to evaluate the CP score and the MELD score for short- and long-term prognosis in cirrhosis, as well as CP-creatinine score, MELD-Na score, and UKELD score. METHODS One thousand and forty-seven patients from five referral centers were included: men/women: 620/427, median age: 58 years (IQR 48-66), median follow-up: 33 months (IQR 12-74), CP (A/B/C): 493/357/147, CP score: 7 (IQR 5-9), MELD score: 12 (IQR 9-16). The performance of each score was evaluated by the Cox hazard model in terms of their: discrimination ability (C-index and Somer's D) and calibration (3, 12 months). Internal validation was done with bootstrapping (100 samples). RESULTS Three hundred and fifty-two patients (33.6%) died. All scores were significantly associated with overall mortality, when assessed by univariate Cox analysis. CP-creatinine score performed significantly better than all other scores [bootstrap C-index 0.672, 95% CI 0.642-0.703, bootstrap Somer's D 0.344 (0.285-0.401)], apart from CP score, which showed similar performance. Inclusion in the multivariable Cox model of age together with CP-creatinine score improved the discriminative ability of the model [bootstrap C-index (95% CI) 0.700 (0.661-0.740)]. In terms of calibration, CP-creatinine score was the best for both 3- and 12-month survival in the total population. CONCLUSIONS CP score and CP-creatinine score have better prognostic value compared to MELD score, MELD-Na score, and UKELD score for predicting short- and long-term mortality in patients with stable cirrhosis.
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Affiliation(s)
- Maria Kalafateli
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece
| | | | - Georgia Vourli
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Cristina Rigamonti
- The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK
| | - John Goulis
- Fourth Department of Internal Medicine, Aristotle University Medical School, Hippokration General Hospital of Thessaloniki, Thessaloníki, Greece
| | - Emanuel Manesis
- Second Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, Athens, Greece
| | - Spilios Manolakopoulos
- Second Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, Athens, Greece
| | - Emmanuel Tsochatzis
- The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, UK
| | | | | | | | - Charalambos Gogos
- Department of Internal Medicine, University Hospital of Patras, Patras, Greece
| | - Giota Touloumi
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Evangelos Akriviadis
- Fourth Department of Internal Medicine, Aristotle University Medical School, Hippokration General Hospital of Thessaloniki, Thessaloníki, Greece
| | | | - Christos Triantos
- Department of Gastroenterology, University Hospital of Patras, Patras, Greece.
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Fortune B, Cardenas A. Ascites, refractory ascites and hyponatremia in cirrhosis. Gastroenterol Rep (Oxf) 2017; 5:104-112. [PMID: 28533908 PMCID: PMC5421465 DOI: 10.1093/gastro/gox010] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 03/09/2017] [Indexed: 02/06/2023] Open
Abstract
Ascites is the most common complication related to cirrhosis and is associated with increased morbidity and mortality. Ascites is a consequence of the loss of compensatory mechanisms to maintain the overall effective arterial blood volume due to worsening splanchnic arterial vasodilation as a result of clinically significant portal hypertension. In order to maintain effective arterial blood volume, vasoconstrictor and antinatriuretic pathways are activated, which increase overall sodium and fluid retention. As a result of progressive splanchnic arterial vasodilation, intestinal capillary pressure increases and results in the formation of protein-poor fluid within the abdominal cavity due to increased capillary permeability from the hepatic sinusoidal hypertension. In some patients, the fluid can translocate across diaphragmatic fenestrations into the pleural space, leading to hepatic hydrothorax. In addition, infectious complications such as spontaneous bacterial peritonitis can occur. Eventually, as the liver disease progresses related to higher portal pressures, loss of a compensatory cardiac output and further splanchnic vasodilation, kidney function becomes compromised from worsening renal vasoconstriction as well as the development of impaired solute-free water excretion and severe sodium retention. These mechanisms then translate into significant clinical complications, such as refractory ascites, hepatorenal syndrome and hyponatremia, and all are linked to increased short-term mortality. Currently, liver transplantation is the only curative option for this spectrum of clinical manifestations but ongoing research has led to further insight on alternative approaches. This review will further explore the current understanding on the pathophysiology and management of ascites as well as expand on two advanced clinical consequences of advanced liver disease, refractory ascites and hyponatremia.
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Affiliation(s)
- Brett Fortune
- Department of Gastroenterology and Hepatology, Weill Cornell Medical College, NY, USA
| | - Andres Cardenas
- Institut de Malalties Digestives i Metabolique, Hospital Clinic, University of Barcelona, Barcelona, Spain
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40
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Ling Q, Dai H, Zhuang R, Shen T, Wang W, Xu X, Zheng S. Predicting short-term survival after liver transplantation on eight score systems: a national report from China Liver Transplant Registry. Sci Rep 2017; 7:42253. [PMID: 28198820 PMCID: PMC5304182 DOI: 10.1038/srep42253] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 01/08/2017] [Indexed: 12/16/2022] Open
Abstract
To compare the performance of eight score systems (MELD, uMELD, MELD-Na. iMELD, UKELD, MELD-AS, CTP, and mCTP) in predicting the post-transplant mortality, we analyzed the data of 6,014 adult cirrhotic patients who underwent liver transplantation between January 2003 and December 2010 from the China Liver Transplant Registry database. In hepatitis B virus (HBV) group, MELD, uMELD and MELD-AS showed good predictive accuracies at 3-month mortality after liver transplantation; by comparison with other five models, MELD presented the best ability in predicting 3-month, 6-month and 1-year mortality, showing a significantly better predictive ability than UKELD and iMELD. In hepatitis C virus and Alcohol groups, the predictive ability did not differ significantly between MELD and other models. Patient survivals in different MELD categories were of statistically significant difference. Among patients with MELD score >35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one. In conclusion, MELD is superior to other score systems in predicting short-term post-transplant survival in patients with HBV-related liver disease. Among patients with MELD score >35, a new prognostic model can identify the sickest patients who should be excluded from waiting list to prevent wasteful transplantation.
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Affiliation(s)
- Qi Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haojiang Dai
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Runzhou Zhuang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian Shen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative innovation center for diagnosis and treatment of infectious diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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41
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Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum Biomarker in Liver Transplant Recipients. Can J Gastroenterol Hepatol 2017; 2017:4381864. [PMID: 28409147 PMCID: PMC5376470 DOI: 10.1155/2017/4381864] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2015] [Accepted: 06/13/2015] [Indexed: 12/29/2022] Open
Abstract
Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period. Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT. Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1-10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92-5.36, p < 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72-3.09; p < 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09-2.01; p = 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank: p < 0.001). Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.
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Enescu A, Petrescu F, Mitruţ P, Pădureanu V, Petrescu OI, Albu VC, Moraru AL, Enescu AŞ. Hyponatremia - unfavourable prognostic factor in hepatic cirrhosis. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2016; 54:207-210. [PMID: 28002032 DOI: 10.1515/rjim-2016-0036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Indexed: 11/15/2022]
Abstract
Hyponatremia is defined by a level of Na in serum below or equal to 136 mEq/L while in hepatic cirrhosis it is classically considered as relevant only at a level of Na below 130 mEq/L. Hyponatremia frequently occurs in patients with end-stage hepatic disease. The frequency and severity are variable but it has been estimated that it occurs with a frequency of 57% in hospitalized patients with cirrhosis and in those on waiting lists for hepatic transplants. Signs and symptoms of hyponatremia are related to dysfunctions of the central nervous system, due to migration of the water from intravascular space to the brain cells, resulting in the occurrence of cerebral edema. Therapeutic options in hyponatremia are limited and are based on restriction of water consumption, exclusion of diuretics and vaptans. Hepatic transplant remains the only definitive treatment for end-stage hepatic diseases in which hyponatremia has occurred.
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43
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Influence of preoperative sodium concentration on outcome of patients with hepatitis B virus cirrhosis after liver transplantation. Eur J Gastroenterol Hepatol 2016; 28:1210-5. [PMID: 27362549 DOI: 10.1097/meg.0000000000000690] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Whether preoperative serum sodium concentration could influence post-transplant patients' prognosis remains controversial. The aim of this study was to evaluate the influence of patients' pretransplant sodium concentration on the prognosis after liver transplantation in a cohort of patients with hepatitis B virus-related cirrhosis. PATIENTS AND METHODS Data derived from the Chinese Liver Transplantation Registry system from 1 January 2000 to 31 December 2011 were extracted. The serum sodium concentrations and model for end-stage liver disease scores were recorded at listing before liver transplantation, and the relationship between the above parameters and patients' outcome was analyzed. RESULTS A total of 2733 patients were included in this study. Compared with patients in the normal group (serum sodium between 135 and 150 mmol/l), patients in the severe hyponatremia group (<125 mmol/l) (P=0.022) and hypernatremia group (>150 mmol/l) (P=0.008) had a poorer prognosis. No significant differences were found among the moderate hyponatremia group (125-130 mmol/l) (P=0.113) and the mild hyponatremia group (130-135 mmol/l) (P=0.461). The 5-year cumulative survivals for the hyponatremia (≤135 mmol/l), normal (135-150 mmol/l), and hypernatremia (≥150 mmol/l) pretransplant group are 79.52, 82.23, and 69.30%, respectively. CONCLUSION Our analysis showed that for patients with hepatitis B virus-related cirrhosis in mainland China, patients with abnormal serum sodium concentrations have poorer prognosis; both preoperative hyponatremia and hypernatremia were identified as negative risk factors for patients' outcome.
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44
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Bittencourt PL, Terra C, Parise ER, Farias AQ, Arroyo V, Fernandez J, Pereira G, Maubouisson LM, Andrade GM, Costa FGDB, Codes L, Andrade AR, Mattos AAD, Torres A, Couto F, Zyngier I. Intensive care management of patients with liver disease: proceedings of a single-topic conference sponsored by the Brazilian Society of Hepatology. ARQUIVOS DE GASTROENTEROLOGIA 2016; 52 Suppl 1:55-72. [PMID: 26959806 DOI: 10.1590/s0004-28032015000500004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Survival rates of critically ill patients with liver disease has sharply increased in recent years due to several improvements in the management of decompensated cirrhosis and acute liver failure. This is ascribed to the incorporation of evidence-based strategies from clinical trials aiming to reduce mortality. In order to discuss the cutting-edge evidence regarding critical care of patients with liver disease, a joint single topic conference was recently sponsored by the Brazilian Society of Hepatology in cooperation with the Brazilian Society of Intensive Care Medicine and the Brazilian Association for Organ Transplantation. This paper summarizes the proceedings of the aforementioned meeting and it is intended to guide intensive care physicians, gastroenterologists and hepatologists in the care management of patients with liver disease.
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Affiliation(s)
- Paulo Lisboa Bittencourt
- Hospital Português, Salvador, Brazil.,Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - Carlos Terra
- Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, RJ, Brazil
| | | | - Alberto Queiroz Farias
- Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | | | - Gustavo Pereira
- Departamento de Gastroenterologia, Hospital Federal do Bonsucesso, Rio de Janeiro, RJ, Brasil
| | | | | | | | - Liana Codes
- Hospital Português, Salvador, Brazil.,Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - Antônio Ricardo Andrade
- Hospital Português, Salvador, Brazil.,Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brasil
| | | | - André Torres
- Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro, RJ, Brazil
| | - Fernanda Couto
- Departamento de Gastroenterologia, Hospital Federal do Bonsucesso, Rio de Janeiro, RJ, Brasil
| | - Ivan Zyngier
- Departamento de Gastroenterologia, Hospital Federal do Bonsucesso, Rio de Janeiro, RJ, Brasil
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45
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Hyponatremia in patients with liver diseases: not just a cirrhosis-induced hemodynamic compromise. Hepatol Int 2016; 10:762-72. [PMID: 27328847 DOI: 10.1007/s12072-016-9746-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 05/27/2016] [Indexed: 12/19/2022]
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46
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Lizaola B, Bonder A, Tapper EB, Mendez-Bocanegra A, Cardenas A. The Changing Role of Sodium Management in Cirrhosis. ACTA ACUST UNITED AC 2016; 14:274-84. [DOI: 10.1007/s11938-016-0094-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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47
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Gisby M, Lundberg J, Ländin M, O'Reilly K, Robinson P, Sobocki P, Jamookeeah C. The burden of illness in patients with hyponatraemia in Sweden: a population-based registry study. Int J Clin Pract 2016; 70:319-29. [PMID: 26997295 DOI: 10.1111/ijcp.12768] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Hyponatraemia (HN; serum sodium level < 135 mmol/l) is the most common electrolyte disturbance seen in clinical practice, and is associated with varying spectrum of symptoms. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common aetiology in hospitalised patients, and can be caused by several different underlying conditions. AIMS The objectives of this study were to retrospectively examine the baseline characteristics, clinical outcomes and hospital resource utilisation of patients with HN and/or SIADH in Sweden over a 10-year period from 2001 to 2011. Additional analysis was performed on subpopulations of patients with hip fracture, pneumonia and small cell lung cancer (SCLC) to see if trends in outcomes were consistent across a broad range of aetiologies commonly associated with the condition. METHODS Patient information was taken from the Swedish National Patient Registry, the Swedish Cancer Registry, the Swedish Cause of Death Register and the Swedish Prescribed Drug Register. A total of 34,537 patients (4.38%) were identified with HN and/or SIADH, with the incidence and prevalence rising over the 10-year study period. RESULTS Of the 34,537 patients identified, 841 had hip fracture, 2635 had pneumonia and 106 had SCLC. Compared with matched control patients, those with HN and/or SIADH had a longer length of hospital stay, a higher re-admission rate and a shorter time to re-admission. CONCLUSIONS This study showed that HN and/or SIADH negatively impact patient outcomes and healthcare resources related to hospital stay irrespective of the underlying cause. The impact of HN is not confined to the initial hospitalisation, as re-admission rates are also affected.
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Affiliation(s)
- M Gisby
- Otsuka Pharmaceutical Europe Limited, Wexham, UK
| | - J Lundberg
- Otsuka Pharma Scandinavia AB, Stockholm, Sweden
| | - M Ländin
- Otsuka Pharma Scandinavia AB, Stockholm, Sweden
| | - K O'Reilly
- Otsuka Pharmaceutical Europe Limited, Wexham, UK
| | - P Robinson
- Otsuka Pharmaceutical Europe Limited, Wexham, UK
| | - P Sobocki
- IMS Health, Stockholm, Sweden
- Karolinska Institutet, Solna, Sweden
| | - C Jamookeeah
- Otsuka Pharmaceutical Europe Limited, Wexham, UK
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48
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Lee JJ, Kim YS, Jung HH. Acute serum sodium concentration changes in pediatric patients undergoing cardiopulmonary bypass and the association with postoperative outcomes. SPRINGERPLUS 2015; 4:641. [PMID: 26543775 PMCID: PMC4628041 DOI: 10.1186/s40064-015-1436-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 10/14/2015] [Indexed: 12/01/2022]
Abstract
The objective of this study is to investigate the degree of serum sodium changes and its association with patient outcomes in pediatrics undergoing heart surgery with cardiopulmonary bypass (CPB). We reviewed the medical records of 275 pediatric patients who underwent heart surgery with CPB. Prior to CPB, hyponatremia (≤135 mmol/L) was observed in 21 of 275 patients. After initiation of CPB, serum sodium decreased significantly and severe hyponatermia (≤130 mmol/L) subsequently developed in 32 patients. At the end of CPB, however, hypernatremia (≥145 mmol/L) developed in 86 patients. The degree of acute serum sodium change during CPB was not associated with patient outcomes. However, the patients with preoperative hyponatremia and those with hypernatremia at the conclusion of CPB had longer hospital stays and higher postoperative complication rates. Lower serum sodium prior to CPB and higher serum sodium at the end of CPB, along with age and duration of the operation, were independently associated with worse in-hospital outcomes. Acute and transient hyponatremia occurred frequently after initiation of CPB, and then serum sodium immediately increased above preoperative levels at the end of CPB. Caution is required to avoid serum sodium overcorrection on the conclusion of CPB.
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Affiliation(s)
- Jeong Jin Lee
- Department of Anaesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young-Soon Kim
- Department of Anaesthesiology and Pain Medicine, Seoul Woman's Hospital, Gyeonggi-do, Bucheon, South Korea
| | - Hae Hyuk Jung
- Department of Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, 156 Baekryung-ro Gangwon-do, Chuncheon, 200-722 South Korea
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49
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Nielsen MJ, Lehmann J, Leeming DJ, Schierwagen R, Klein S, Jansen C, Strassburg CP, Bendtsen F, Møller S, Sauerbruch T, Karsdal MA, Krag A, Trebicka J. Circulating Elastin Fragments Are Not Affected by Hepatic, Renal and Hemodynamic Changes, But Reflect Survival in Cirrhosis with TIPS. Dig Dis Sci 2015; 60:3456-64. [PMID: 26138655 DOI: 10.1007/s10620-015-3783-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Accepted: 06/21/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS). METHODS We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated. RESULTS Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients. CONCLUSION This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.
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Affiliation(s)
- M J Nielsen
- Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark.,Department of Gastroenterology, Odense Hospital, University of Southern Denmark, Odense, Denmark
| | - J Lehmann
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - D J Leeming
- Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark
| | - R Schierwagen
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - S Klein
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - C Jansen
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - C P Strassburg
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - F Bendtsen
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - S Møller
- Department of Clinical Physiology and Nuclear Medicine, 239 Center for Functional and Diagnostic Imaging and Research, Faculty of Health Sciences Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
| | - T Sauerbruch
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
| | - M A Karsdal
- Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark
| | - A Krag
- Department of Gastroenterology, Odense Hospital, University of Southern Denmark, Odense, Denmark
| | - J Trebicka
- Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
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Predictors of Early Hospitalization After Deceased Donor Liver Transplantation. Dig Dis Sci 2015; 60:3242-7. [PMID: 26123837 PMCID: PMC4743740 DOI: 10.1007/s10620-015-3753-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 06/06/2015] [Indexed: 12/09/2022]
Abstract
UNLABELLED Hospitalizations after solid organ transplantation may affect patient outcomes. Identification of the factors attributed to them may decrease hospitalization rates, reduce overall cost, and improve post-transplant outcomes. We examined the risk factors for early hospitalization within 30 and 90 days after liver transplantation (LT). METHODS Data on all deceased donor LT recipients (age ≥18 years) transplanted between 2/28/2002-2/27/2007 and discharged alive from the index hospitalization within 30 days of LT were collected (N = 267). Patients were followed up until December 31, 2013. Logistic regression was used to identify the predictors of 30-day hospitalization, and linear regression was used to identify the factors associated with number of days hospitalized during 30- and 90-day hospitalization after LT. Renal risk index (RRI), a recently developed and validated risk score that accurately predicts the post-LT ESRD based upon recipient factors at LT, was computed using RRI calculator ( http://rri.med.umich.edu ). RESULTS One-third and more than half of the patients had at least one 30- and 90-day hospitalization, respectively. RRI decile (OR 1.12, P = 0.02) and serum sodium at LT (OR 0.90, P < 0.001) were independently associated with 30-day hospitalization after adjusting for MELD score. Serum creatinine at LT (β = 4.34, P = 0.001) and pre-LT admission days (β = 0.15, P = 0.027) affected the number of days hospitalized for 90-day hospitalization. RRI was also an independent predictor of post-LT mortality. CONCLUSION Early hospitalizations within 30 and 90 days after deceased donor LT are common. While all post-LT hospitalization cannot be prevented, efforts should be directed toward risk-based post-discharge care, and coordination of effective transitional care through ambulatory clinics. Implementation of such processes may attenuate early post-LT hospitalization and resource utilization and improve quality.
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